PROJECT SUMMARY Glaucoma is a major problem worldwide, with 60 million people currently affected and 112 million expected by 2040. At present, the primary treatment of glaucoma relies on medication administered as topical eye drops, with prostaglandin analogues, as the first-line therapy, representing 51% of total prescriptions. However, eye drops present significant limitations in bioavailability due to tear drainage, and a poor patient adherence rate of 50% amongst those with a daily drop regimen. Second-line drops require even more frequent dosing per day and hence worse adherence to the therapy is observed. We propose to develop a drug-delivering contact lens (DDCL) with extended wear and sustained drug release of up to 7 days for the treatment of open-angle glaucoma. The goal is to replace topical eye drops as the standard of care for glaucoma. Key advantages of the DDCL will be lower dosing frequency, direct delivery to the corneal surface at a constant rate, high-precision dosing and targeting, all by a cost-competitive lens device. The specific aims of this project are summarized as a DDCL device capable of (a) Releasing bimatoprost at a consistent rate, day and night for 7-days, (b) Achieving the highest precision in delivery dosage and target location, (c) being the best-in-class contact lens (i.e. Dk ~ 140, tear turnover cycle < 15 min., low contact angle, and easy to handle) for improving the long-term (7 days) wearing comfort, adherence, and safety. In the proposed Phase II work plan, we want to implement these improvements and evaluate efficacy using animal model studies. The proposed DDCL will not only resolve all the deficiencies of eye drop administration, but also could set a new standard against other competing technologies of ocular bandages, injectable polymers, surgical implants, etc. in the following categories: (a) The accurate control of drug release rate between first to zero order kinetics throughout the delivery duration, (b) The precise dosing of bioavailable drug amount based on matching rates of drug discharge, tear turnover and corneal adsorption, (c) The lens material innovation required for 7-day wearing comfort, safety, easy of handling (by elderlies), and at a competitive cost. After Phase II, we plan to seek regulatory approval with an IND, human clinical trials, and an NDA.